Nursing 2023 Discussion: Foundational Neuroscience
TO DO A REPLY COMMENT TO POST 1 and 2 WITH TWO APA REFERENCES EACH ABOVE 2013 POST 1 2023 Assignment
TO DO A REPLY COMMENT TO POST 1 and 2 WITH TWO APA REFERENCES EACH ABOVE 2013.
An agonist to antagonist to inverse agonist spectrum
Psychoactive medications vary in how they affect activity at the synapse. Agonists increase the neurotransmitter effect while antagonists block the neurotransmitter effect (Barron, 2018). There are gradients of how medications act creating a spectrum of influence on receptors. Agonists can occur naturally as neurotransmitters that stimulate receptors. Some medications also act as agonists to stimulate receptors, but medications can stimulate receptors to varying degrees (Stahl, 2013). This creates the spectrum of how medications variably affect neurotransmitters. The medications that stimulate receptors but do so less than full agonists are partial agonists or stabilizers. Antagonists have no activity of their own except to block the activity of the agonists, sometimes antagonists are called silent (Stahl, 2013). At the opposite end of the spectrum from agonists are inverse agonists. These medications block agonists and decrease activity to below the normal baseline level when there is no agonist present (Stahl, 2013).
G Couple proteins and Ion gated channels
Ion gated channels are proteins that form pores in cell membranes (Inanobe & Kurachi, 2014). These pores are the channels that allow movement across the cell membrane and are controlled by several mechanisms. The pore may open due to the voltage difference across the membrane (Ianonobe & Kurachi, 2014). Ligand-gated channels have a domain extracellular that associates with small chemicals and regulatory proteins (Ianonobe & Kurachi, 2014). A domain is a protein that has its own stable structure (Genscript, 2018). Ion channels gated by ligands can be opened or closed by a neurotransmitter that is specific to a ligand binding and causing a very short, brief open active state that occurs in milliseconds (Inanobe & Kurachi, 2014). The ligand-gated channels can also be opened when metabotropic receptors that have G protein-coupled receptors are stimulated by G protein signaling (Inanobe & Kurachi, 2014). The G protein-coupled ion gated open response is slower and is longer lived than the neurotransmitter ion channel opening (Ianonobe & Kurachi, 2014). In summary, an ion gated channel is a throughway to the cell and this throughway is stimulated to be opened or closed by various mechanisms. One of the ways the ion gated channel is stimulated to open is through G couple proteins.
Epigenetics in pharmacologic action
Genes are inherited from each parent. But epigenetics looks at if the gene is developed into its specific RNA and protein or if the gene is silenced and ignored (Stahl, 2013). Childhood stress has been found to deactivate the receptors for glucocorticoids (Rosenfield & Ziff, 2018). Because the receptors are deactivated people grow up with disrupted feedback. The glucocorticoids continue to be made by the body in greater amounts because they are not detected normally. DNA methylation occurs and creates a barrier to normal genetic codes (Rosenfield & Ziff, 2018). Long-term effects from childhood stressors are chronic inflammation, diabetes, heart disease, obesity, schizophrenia and major depressive disorder (Rosenfield & Ziff, 2018). Cells including neurons respond to life stressors by reacting to genetics. Genes may be silenced or activated but the expression of genetics can vary depending on stress (Stahl, 2013).
Possible Impact on Clients
Psychopharmacology is important because of the impact interactions can have on patients. As future prescribers, it is important to be aware of patient differences and how illness affect patient’s ability to metabolize medications (Laureate Education, 2012). It is also important to be aware of drug interactions with other medications, foods, and metabolism. For example, Wellbutrin is primarily metabolized by CYP2B6. So, Wellbutrin can react with other medications that are inhibitors or inducers of CYP2B6 (Drugs.com, 2018). Plavix and Ticlid are CYP2B6 inhibitors and can increase bupropion levels (Drugs.com, 2018). People also metabolize medications differently. There are four classes of metabolizers from ultra-extensive metabolizers to poor metabolizers (Barron, 2018). Knowing the type of metabolizer that the patient is can be helpful in tailoring their medication and dosage. Epigenetics teaches us that people with trauma can have their gene expression altered by DNA methylation. Trauma can lead to metabolic type diseases as well as depression and schizophrenia. As a client example, a 17-year-old male was admitted for being increasingly physically and verbally abusive to his entire foster family. The client had pushed down a foster brother and punched and kicked his foster mom and dad. This client had been taken away from his biological mom around age 5 due to her drug use, neglect then jail. He was then placed with his maternal grandmother who could not handle his behavior. The client then was placed in numerous foster homes for brief periods of time. He acted appropriately in the Psychiatric care center, so he could control his behavior when multiple security/ authority figures were present. The client had been on Wellbutrin at home and when he had symptoms of insomnia and aggression his Wellbutrin was increased. He was taken off Wellbutrin and started on another medication. Some of the more common side effects of Wellbutrin are sleep disturbance (45%), agitation (32%), irritability, and anxiety (Drugs.com, 2018). This patient’s history of trauma and aggression set him up for depression, anxiety and irritability then when he had increased symptoms with the medication it was increased to the maximum dose as an outpatient. He became increasingly agitated and then violent which led to his admission to an inpatient psychiatric facility.
Barron, S. (2018). Psychopharmacology. Nobia textbook series: Psychology. https://doi.org/nobaproject
Drugs.com. (2018). Wellbutrin. Retrieved from https://www.drugs.com/pro/wellbutrin.html
Genscript. (2018). Domain. Retrieved from https://www.genscript.com/molecular-biology-glossary/819/domain
Inanobe, A., & Kurachi, Y. (2014, February). Membrane channels as integrators of G-protein mediated signaling. Biochimica et Biophysica Acta (BBA) Biomembranes, 1838(2), 521-531. https://doi.org/10.1016/j.bbamem.2013.08.018
Laureate Education. (2012). Introduction to advanced pharmacology[Video file]. Retrieved from Walden University
Rosenfield, I., & Ziff, E. (2018). Epigenetics: The evolution revolution. Retrieved from https://www.nybooks.com/articles/2018/06/07/epigenetics-the-evolution-revolution/
Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). Retrieved from https://stahlonline-cambridge-org.ezp.waldenulibrary.org
Agonist to Antagonist Spectrum
Most drugs act as either agonists or antagonists at receptors in response to chemical messages in the brain. An agonist, which can be described as partial or inverse, binds to the receptor to produce an effect. Antagonists also bind to receptors but does not produce a response, rather blocks that receptor to a natural agonist (Pleuvry, 20004). It is important to acknowledge that agonists and inverse agonists can be reversed by competitive antagonists. In reference to atypical psychotropic drugs (APD), the blockade of serotonin receptors (5-HT2A) along with the weak antagonism of dopamine receptor (D2) is critical in potency and efficacy, as typical APD have tendency to antagonize D2 receptors more potently than 5-HT2A receptors (Kusumi, Boku, & Takahashi, 2014).
G-coupled Protein and Ion-gated Channels
G-protein linked receptors are important to clinicians with to target specific receptors with psychotropic drugs (Stahl, 2013). Nonetheless, all agonists do not produce an active state of G-protein-coupled-receptors as in constitutive activity of receptors for benzodiazepines, serotonin, and other G-protein linked receptors. Contrarily, ion channels function as a result of neurotransmitter ligands at receptors. Numerous drugs act at ion-channel complexes altering flow of ions through the channels due to the transduction of the signal at receptors (Stahl, 2013). As a result of the changes of flow of ions, drugs that act on ionotropic receptors tend to act immediately while G-protein linked receptors act at lower frequencies.
Epigenetics in Pharmacologic Action
The lack of response to standard therapies in certain individuals because of various molecular alterations can be due to genetic heterogenecity and epigenetic alterations (Rasool et al., 2015). Epigenetic modifications can occur as a result of various chemical compounds in the biological system, changing gene expression. Environmentally and biologically influenced alterations can lead to disorders, therefore clients with epigenetic alterations may require drugs used for personalized medicine based on their personal genomic profile.
Impact on How Medicine is Prescribed
Understanding the agonistic/antagonistic effects of medications along with the prescribing of medications specific to G-protein coupled receptors, and personalized medication profiles required by epigenetic alterations found in certain cases is important to PMHNP’s who may prescribe psychotropic medications to these clients. Studies have found an existence of constitutive receptor activity in benzodiazepine receptors and G-protein coupled receptors and may be present in mutated strains exhibiting underactive behavior that can lead to inherited diseases such as congenital hypothyroidism and diabetes insipidus (Rasool et al., 2015). For schizophrenic clients at greater risk for developing extrapyramidal symptoms (EPS), it is known that risperidone equally occupies D2 and 5-HT2A receptors increasing the frequency of EPS, while clozapine more potently occupies 5-HT2A receptors than D2 receptors, rarely producing EPS (Kusumi, Boku, & Takahashi, 2014). It is the responsibility of the PMHNP to understand their clients’ profiles and medical histories in order to properly prescribe the most effective medications with the least adverse effects.
Kusumi, I., Boku, S., & Takahashi, Y. (2014). Psychopharmacology of atypical antipsychotic drugs: From the recpetor binding profile to neuroprotection and neurogenesis. Psychiatry and Clinical Neurosciences, 69(5): 243-258. doi: 10.1111/pcn.12242.
Pleuvry, B. (2004). Receptors, agonists, and antagonists. Anaesthesia & Intensive Care Medicine, 5(10): 350-352. doi: 10.1383/anes.5.10.350.52312.
Rasool, M., Malik, A., Naseer, M., Manan, A., Ansari, S., Begum, I.,…Gan, S. (2015). The role of epigenetics in personalized medicine: Challenges and opportunites. BMC Medical Genomics, 8(Suppl 1): S5. doi: 10.1186/1755-8794-8-S1-S5.
Stahl, S. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press.
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